One of the most exciting developments in environmental science and technology is the emerging field of exposomics, i.e., rapid and sensitive detection of large sets of analytes (exposome) reflecting the complexity of exposure in the personal environment using human specimens including blood, urine, and saliva, which are likely to be available from both prospective and retrospective epidemiological cohorts. However, technology platforms that could perform high-sensitivity, high-specificity, and multi-analyte detection of these samples, particularly in small volumes, are currently lacking. Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) is the most powerful technique for large-scale quantitative and qualitative analyses of proteins and metabolites, i.e., proteomics and metabolomics. Although a variety of mass spectrometry approaches have been used in the National Biomonitoring Program (NBP), they typically require relatively large sample volumes for plasma and serum analyses because of the extremely low concentrations of target analytes. This renders them impractical for population studies of multiple analytes where very small volumes of blood are collected and stored. In response to RFA-ES-14-005, Newomics Inc. proposes this SBIR Phase II project to complete development of its product, the fully-integrated silicon microfluidic chips, as a new platform for rapid and sensitive biomonitoring of multiple and multiclass analytes. The project is built upon the extremely promising results generated from our SBIR Phase I project. Our novel microchips monolithically interface solid-phase extraction (SPE) with liquid chromatography (LC)-nanoelectrospray mass spectrometry (nanoESI-MS) on a single device. The SPE-LC-MS chips, which we term Biomonitoring Chips, will serve as a low-cost universal platform for enabling high-sensitivity, high-specificity, high-throughput, multiplexed, and multi-analyte biomonitoring using small volumes of biospecimens including blood samples. Our biomonitoring chips will offer new opportunities for epidemiologic studies which seek to characterize individual exposomes through MS-based metabolomics, proteomics, and adductomics analyses of diverse classes of analytes in human biospecimens.